Desaturation and elongation are necessary steps in the modification of the essential fatty acids EFA), linoleic (18:2n6) and linolenic (18:3n3) acids, to arachidonic (20:4n6) and docosahexaenoic (22:6n3) acids, respectively. The levels of the latter two fatty acids are lowered by ethanol consumption in blood cells, liver and brain in animals. We have shown that the mechanisms underlying the disruption of essential fatty acid levels in these tissues are in part due to the inhibition of the elongation/desaturation of 18-carbon essential fatty acids by alcohol. A stable isotope gas chromatography-mass spectrometry (GC-MS) method has been developed that allows for the in vivo examination of these processes. This method has improved the sensitivity of studies in large animals. Studies in mice, rats, cats and rhesus monkeys have suggested that all mammals have elongation and desaturation capability and that heir products may be monitored in the blood supply. Felines, which had been given alcohol for 14 weeks, showed an 80% reduction in 20:4n6 and eicosapentaenoic (20:5n3) acid in the liver and blood together with a decrease in the metabolism of deuterated 18:2n6 and 18:3n3 to deuterated 20:4n6 and 20:5n3, respectively. Our findings show that the feline brain is a unique site of 22:6n3 production in this species, therefore, we are investigating the effects of chronic alcohol exposure on the brain's lipid composition and 22:6n3 formation. Our recent studies indicate specific fats in the diet regulate the synthesis of polyunsaturated fatty acids in carnivores and non-human primates. We have initiated human trials to investigate the effects of diet, and alcohol withdrawal on essential fatty acid metabolism.